Association between Polymorphism of Genes IL-1A, NFKB1, PAR1, TP53, and UCP2 and Susceptibility to Non-Small Cell Lung Cancer in the Brazilian Amazon.

Non-small cell lung cancer (NSCLC) accounts for the vast majority of cases of lung neoplasms. It is formed in multiple stages, with interactions between environmental risk factors and individual genetic susceptibility and with genes involved in the immune and inflammatory response paths, cell or genome stability, and metabolism, among others. Our objective was to evaluate the association between five genetic variants (IL-1A, NFKB1, PAR1, TP53, and UCP2) and the development of NSCLC in the Brazilian Amazon. The study included 263 individuals with and without lung cancer. The samples were analyzed for the genetic variants of NFKB1 (rs28362491), PAR1 (rs11267092), TP53 (rs17878362), IL-1A (rs3783553), and UCP2 (INDEL 45-bp), which were genotyped in PCR, followed by an analysis of the fragments, in which we applied a previously developed set of informative ancestral markers. We used a logistic regression model to identify differences in the allele and the genotypic frequencies among individuals and their association with NSCLC. The variables of gender, age, and smoking were controlled in the multivariate analysis to prevent confusion by association. The individuals that were homozygous for the Del/Del of polymorphism NFKB1 (rs28362491) (p = 0.018; OR = 0.332) demonstrate a significant association with NSCLC, which was similar to that observed in the variants of PAR1 (rs11267092) (p = 0.023; OR = 0.471) and TP53 (rs17878362) (p = 0.041; OR = 0.510). Moreover, the individuals with the Ins/Ins genotype of polymorphism IL-1A (rs3783553) demonstrated greater risk for NSCLC (p = 0.033; OR = 2.002), as did the volunteers with the Del/Del of UCP2 (INDEL 45-bp) (p = 0.031; OR = 2.031). The five polymorphisms investigated can contribute towards NSCLC susceptibility in the population of the Brazilian Amazon.

The Role of SLC22A1 and Genomic Ancestry on Toxicity during Treatment in Children with Acute Lymphoblastic Leukemia of the Amazon Region.

In Brazil, Acute lymphoid leukemia (ALL) is the leading cause of cancer deaths in children and adolescents. Treatment toxicity is one of the reasons for stopping chemotherapy. Amerindian genomic ancestry is an important factor for this event due to fluctuations in frequencies of genetic variants, as in the NUDT15 and SLC22A1 genes, which make up the pharmacokinetic and pharmacodynamic pathways of chemotherapy. This study aimed to investigate possible associations between NUDT15 (rs1272632214) and SLC22A1 (rs202220802) gene polymorphism and genomic ancestry as a risk of treatment toxicities in patients with childhood ALL in the Amazon region of Brazil. The studied population consisted of 51 patients with a recent diagnosis of ALL when experiencing induction therapy relative to the BFM 2009 protocol. Our results evidenced a significant association of risk of severe infectious toxicity for the variant of the SLC22A1 gene (OR: 3.18, p = 0.031). Genetic ancestry analyses demonstrated that patients who had a high contribution of African ancestry had a significant protective effect for the development of toxicity (OR: 0.174; p = 0.010), possibly due to risk effects of the Amerindian contribution. Our results indicate that mixed populations with a high degree of African ancestry have a lower risk of developing general toxicity during induction therapy for ALL. In addition, individuals with the SLC22A1 variant have a higher risk of developing severe infectious toxicity while undergoing the same therapy.

UGT1A1 Gene Polymorphism Contributes as a Risk Factor for Lung Cancer: A Pilot Study with Patients from the Amazon.

Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a UGT1A1 gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the UGT1A1 gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (p = 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (p = 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (p = 0.015; OR: 4.08). Polymorphism in the UGT1A1 gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.

Association between INDELs in MicroRNAs and Susceptibility to Gastric Cancer in Amazonian Population.

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.